Discovery of 2,4-dimethoxypyridines as novel autophagy inhibitors

作者：Robke Lucas; Rodrigues Tiago; Schroeder Peter; Foley Daniel J; Bernardes Goncalo J L; Laraia Luca^*; Waldmann Herbert^*

来源：Tetrahedron, 2018, 74(35): 4531-4537.

DOI：10.1016/j.tet.2018.07.021

• Autophagy
• Phenotypic screening
• High-throughput screening
• Natural products
• Medicinal chemistry

Autophagy is a catabolic process, which mediates degradation of cellular components and has important roles in health and disease. Therefore, small molecule modulators of autophagy are in great demand. Herein, we describe a phenotypic high-content screen for autophagy inhibitors, which led to the discovery of a dimethoxypyridine-based class of autophagy inhibitors, which derive from previously reported, natural product-inspired MAP4K4 inhibitors. Comprehensive structure-activity relationship studies led to a potent compound, and biological validation experiments indicated that the mode of action was upstream or independent of mTOR.

• 出版日期2018-8-30
• 单位河北医科大学